Field of the Invention
The invention generally relates to improved methods of adenoviral cancer therapy. In particular, the invention provides adenoviral vectors that are Coxsackie Adenoviral Receptor (CAR) independent, cancer-specific in their replication and produce a systemically active anti-cancer cytokine.
Background
Adenoviral vectors have shown great promise with respect to the delivery and expression of therapeutic agents to cells. However, to date, the level of infectivity, and hence the efficacy, of adenoviral vectors is determined by the presence, in the targeted cells, of Coxsackie Adenoviral Receptors (CARs), which mediate viral entry into the cell. In this regard, it is particularly unfortunate that many types of cancer cells express low or no appreciable levels of CARs. This feature of cancer cells severely curtails the otherwise promising use of adenoviral vectors as anticancer agents. Additionally, an ability to selectively replicate in cancer cells and also produce a therapeutically active and safe secreted cytokine will limit non-specific toxicity and allow for treatment of both primary infected tumors and distant infected or non-infected metastases.